title: Broad-spectrum antivirals for the emerging Middle East respiratory syndrome coronavirus.
abstract: OBJECTIVE
  Middle East respiratory syndrome coronavirus (MERS-CoV) has emerged to cause fatal infections in patients in the Middle East and traveler-associated secondary cases in Europe and Africa. Person-to-person transmission is evident in outbreaks involving household and hospital contacts. Effective antivirals are urgently needed.
  
  
  METHODS
  We used small compound-based forward chemical genetics to screen a chemical library of 1280 known drugs against influenza A virus in Biosafety Level-2 laboratory. We then assessed the anti-MERS-CoV activities of the identified compounds and of interferons, nelfinavir, and lopinavir because of their reported anti-coronavirus activities in terms of cytopathic effect inhibition, viral yield reduction, and plaque reduction assays in Biosafety Level-3 laboratory.
  
  
  RESULTS
  Ten compounds were identified as primary hits in high-throughput screening. Only mycophenolic acid exhibited low EC50 and high selectivity index. Additionally, ribavirin and interferons also exhibited in-vitro anti-MERS-CoV activity. The serum concentrations achievable at therapeutic doses of mycophenolic acid and interferon-β1b were 60-300 and 3-4 times higher than the concentrations at which in-vitro anti-MERS-CoV activities were demonstrated, whereas that of ribavirin was ∼2 times lower. Combination of mycophenolic acid and interferon-β1b lowered the EC50 of each drug by 1-3 times.
  
  
  CONCLUSIONS
  Interferon-β1b with mycophenolic acid should be considered in treatment trials of MERS.
authors.affiliation: State Key Laboratory of Emerging Infectious Diseases, The University of Hong Kong, Hong Kong, China; Department of Microbiology, The University of Hong Kong, Hong Kong, China; Research Centre of Infection and Immunology, The University of Hong Kong, Hong Kong, China.
authors.forename: Jasper F W
authors.initials: JF
authors.lastname: Chan
authors.forename: Kwok-Hung
authors.initials: KH
authors.lastname: Chan
authors.forename: Richard Y T
authors.initials: RY
authors.lastname: Kao
authors.forename: Kelvin K W
authors.initials: KK
authors.lastname: To
authors.forename: Bo-Jian
authors.initials: BJ
authors.lastname: Zheng
authors.forename: Clara P Y
authors.initials: CP
authors.lastname: Li
authors.forename: Patrick T W
authors.initials: PT
authors.lastname: Li
authors.forename: Jun
authors.initials: J
authors.lastname: Dai
authors.forename: Florence K Y
authors.initials: FK
authors.lastname: Mok
authors.forename: Honglin
authors.initials: H
authors.lastname: Chen
authors.forename: Frederick G
authors.initials: FG
authors.lastname: Hayden
authors.forename: Kwok-Yung
authors.initials: KY
authors.lastname: Yuen
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology*; D002522:Chlorocebus aethiops; D021821:Communicable Diseases, Emerging / Q000188:drug therapy / Q000821:virology*; D017934:Coronavirus / Q000187:drug effects*; D018352:Coronavirus Infections / Q000188:drug therapy / Q000821:virology*; D004196:Disease Outbreaks; D055808:Drug Discovery / Q000379:methods; D057166:High-Throughput Screening Assays / Q000379:methods; D006801:Humans; D007372:Interferons / Q000494:pharmacology; D009173:Mycophenolic Acid / Q000494:pharmacology; D012254:Ribavirin / Q000494:pharmacology; D014709:Vero Cells; D019562:Viral Load / Q000187:drug effects; D010948:Viral Plaque Assay
chemical_list: D000998:Antiviral Agents; D012254:Ribavirin; D007372:Interferons; D009173:Mycophenolic Acid
keywords: Antiviral; Coronavirus; Interferon; Middle East; Mycophenolic acid; Ribavirin